Gilles Simon sprung a surprise on Denis Shapovalov in Cologne, where Diego Schwartzman made serene progress to round three.
Former world number one Andy Murray's return to clay court ended with a chastening straight-sets defeat to Stan Wawrinka at the French Open.
With the draw open after Novak Djokovic's exit, Alexander Zverev and Denis Shapovalov reached the quarter-finals.
Borna Coric and Denis Shapovalov delivered stunning comeback wins at the US Open.
German Alexander Zverev needed more than three hours to reach the US Open second round.
Top seed Novak Djokovic charged through on Tuesday, while Andy Murray lost to Milos Raonic in the last 16.
Stefanos Tsitsipas was untroubled by Kevin Anderson at the Western & Southern Open.
Stefanos Tsitsipas beat Benoit Paire and Richard Gasquet defeated David Goffin at the Ultimate Tennis Showdown.
Daniil Medvedev proved too strong for Jannik Sinner in Marseille, while David Goffin suffered another upset.
Daniil Medvedev was followed out of the Rotterdam Open by Stefanos Tsitsipas and David Goffin on Thursday.